The spare-parts technique: A safe and efficient single-stage nipple and areola reconstruction.

BACKGROUND: The authors hypothesized that optimization of nipple-areolar reconstruction using full-thickness skin graft and cartilage graft can be completed safely in a single-stage procedure. METHODS: A retrospective analysis of abdominal-based flap breast reconstruction patients who underwent nipple-areolar reconstruction (NAR) using the modified double-opposing tab (mDOT)1 flap technique was conducted. Complication rates were compared between patients who underwent NAR in a traditional staged procedure versus a single stage. The single-stage group of patients had NAR performed at the time of revision surgery. Reconstruction was performed with full-thickness skin graft from the abdominal standing-cone deformity and costal cartilage that was removed at the time of breast reconstruction and banked subcutaneously until the revision surgery. RESULTS: In this study, 1,233 nipple reconstructions were reviewed, of which 113 procedures using themDOT technique were analyzed. No significant differences in complication rates were found between the single-stage and the traditional staged NAR, including the risk of total loss of reconstruction or delayed skin graft take. However, the risk of delayed wound healing of the nipple reconstruction was higher in the single-stage group. CONCLUSIONS: Our study shows that optimizing NAR results by adding cartilage to the nipple construct and enhancing the areolar component by full-thickness skin grafting can be achieved safely in a single stage at the time of flap revision. This represents potential for better long-term nipple projection and better areolar texture mimicry of NAR for breast reconstruction patients.

Outcomes of Acellular Dermal Matrix for Immediate Tissue Expander Reconstruction with Radiotherapy: A Retrospective Cohort Study.

BACKGROUND: Despite increasing literature support for the use of acellular dermal matrix (ADM) in expander-based breast reconstruction, the effect of ADM on clinical outcomes in the presence of post-mastectomy radiation therapy (PMRT) has not been well described. OBJECTIVES: To analyze the impact ADM plays on clinical outcomes on immediate tissue expander (ITE) reconstruction undergoing PMRT. METHODS: We retrospectively reviewed patients who underwent ITE breast reconstruction from 2004 to 2014 at MD Anderson Cancer Center. Patients were categorized into four cohorts: ADM, ADM with PMRT, non-ADM, and non-ADM with PMRT. Outcomes and complications were compared among cohorts. RESULTS: Over 10 years, 957 patients underwent ITE reconstruction (683 non-ADM, 113 non-ADM with PMRT, 486 ADM, and 88 ADM with PMRT) with 1370 reconstructions. Overall complication rates for the ADM and non-ADM cohorts were 39.0% and 16.7%, respectively (P < 0.001). Within both cohorts, mastectomy skin flap necrosis (MSFN) was the most common complication, followed by infection. ADM use was associated with a significantly higher rate of infections and seromas in both radiated and non-radiated groups; however, when comparing radiated cohorts, the incidence of explantation was significantly lower with the use of ADM. CONCLUSIONS: The decision to use ADM for expander-based breast reconstruction should be performed with caution, given higher overall rates of complications, including infections and seromas. There may, however, be a role for ADM in cases requiring PMRT, as the overall incidence of implant failure is lower than non-ADM cases.

Direct-to-Implant versus Two-Stage Tissue Expander/Implant Reconstruction: 2-Year Risks and Patient-Reported Outcomes from a Prospective, Multicenter Study.

BACKGROUND: Direct-to-implant breast reconstruction offers time-saving advantages over two-stage techniques. However, use of direct-to-implant reconstruction remains limited, in part, because of concerns over complication rates., The authors' aim was to compare 2-year complications and patient-reported outcomes for direct-to-implant versus tissue expander/implant reconstruction. METHODS: Patients undergoing immediate direct-to-implant or tissue expander/implant reconstruction were enrolled in the Mastectomy Reconstruction Outcomes Consortium, an 11-center prospective cohort study. Complications and patient-reported outcomes (using the BREAST-Q questionnaire) were evaluated. Outcomes were compared using mixed-effects regression models, adjusting for demographic and clinical characteristics. RESULTS: Of 1427 patients, 99 underwent direct-to-implant reconstruction and 1328 underwent tissue expander/implant reconstruction. Two years after reconstruction and controlling for covariates, direct-to-implant and tissue expander/implant reconstruction patients did not show statistically significant differences in any complications, including infection. Multivariable analyses found no significant differences between the two groups in patient-reported outcomes, with the exception of sexual well-being, where direct-to-implant patients fared better than the tissue expander/implant cohort (p = 0.047). CONCLUSIONS: This prospective, multi-institutional study showed no statistically significant differences between direct-to-implant and tissue expander/implant reconstruction, in either complication rates or most patient-reported outcomes at 2 years postoperatively. Direct-to-implant reconstruction appears to be a viable alternative to expander/implant reconstruction. This analysis provides new evidence on which to base reconstructive decisions. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Molecular Profiling Using Breast Cancer Subtype to Plan for Breast Reconstruction.

BACKGROUND: Molecular profiling using breast cancer subtype has an increasing role in the multidisciplinary care of the breast cancer patient. The authors sought to determine the role of breast cancer subtyping in breast reconstruction and specifically whether breast cancer subtyping can determine the need for postmastectomy radiation therapy and predict recurrence-free survival to plan for the timing and technique of breast reconstruction. METHODS: The authors reviewed prospectively collected data from 1931 reconstructed breasts in breast cancer patients who underwent mastectomy between November of 1999 and December of 2012. Reconstructed breasts were grouped by breast cancer subtype and examined for covariates predictive of recurrence-free survival and need for postmastectomy radiation therapy. RESULTS: Of the reconstructed breasts, 753 (39 percent) were luminal A, 538 (27.9 percent) were luminal B, 224 (11.6 percent) were luminal HER2, 143 (7.4 percent) were HER2-enriched, and 267 (13.8 percent) were triple-negative breast cancer. Postmastectomy radiation therapy was delivered in 69 HER2-enriched patients (48.3 percent), 94 luminal HER2 patients (42 percent), 200 luminal B patients (37.2 percent), 99 triple-negative breast cancer patients (37.1 percent), and 222 luminal A patients (29.5 percent) (p < 0.0001). Luminal A cases had better recurrence-free survival than HER2-enriched cases, and triple-negative breast cancer cases had worse recurrence-free survival than HER2-enriched cases. Luminal B and luminal HER2 cases had recurrence-free survival similar to that for HER2-enriched cases. Luminal A subtype was associated with the best recurrence-free survival. Subtyping may have improved the breast surgery planning for 33.1 percent of delayed reconstructions that did not require postmastectomy radiation therapy and 37 percent of immediate reconstructions that did require postmastectomy radiation therapy. CONCLUSION: This study is the first publication in the literature to evaluate breast cancer subtype to stratify risk for decision making in breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Fewer Revisions in Abdominal-based Free Flaps than Latissimus Dorsi Breast Reconstruction after Radiation.

The most commonly chosen flaps for delayed breast reconstruction after postmastectomy radiation therapy (PMRT) are abdominal-based free flaps (ABFFs) and pedicled latissimus dorsi (LD) musculocutaneous flaps. The short-and long-term advantages and disadvantages of delayed ABFFs versus LD flaps after PMRT remain unclear. We hypothesized that after PMRT, ABFFs would result in fewer postoperative complications and a lower incidence of revision surgery than LD flaps. METHODS: We retrospectively reviewed a prospectively maintained database of consecutive patients who underwent unilateral, delayed breast reconstruction after PMRT using ABFFs or pedicled LD flaps with implants at the MD Anderson Cancer Center between January 1, 2001, and December 31, 2011. We compared outcomes and additional surgeries required between the 2 groups. Univariate and multivariate logistic regression modeling analyzed the relationships between patient and reconstruction characteristics and postoperative outcomes. RESULTS: A total of 139 consecutive patients' breast reconstructions were evaluated: 101 ABFFs (72.7%) versus 38 LDs (27.3%). Average follow-up was similar for ABFF and LD reconstructions. Although ABFF and LD reconstructions experienced similar rates of overall (30.7% vs 23.7%, respectively; P = 0.53), donor-site (8.91% vs 5.13%, respectively; P = 0.48), and flap (20.7% vs 17.9%, respectively; P = 0.37) complications, the LD reconstructions required more additional surgeries (92.1% vs 67.3%; P < 0.001). Furthermore, LDs required more revision surgeries more than 1 year after reconstruction (37.1% vs 14.7%; P = 0.02). CONCLUSION: Although early complication rates were similar for both types of reconstructions, ABFFs seem to have the advantage of providing a more durable result that required fewer revision surgeries in the long term.

Salvaging the Infected Breast Tissue Expander: A Standardized Multidisciplinary Approach.

BACKGROUND: Infections of breast tissue expander (TE) are complex, often requiring TE removal and hospitalization, which can delay further adjuvant therapy and add to the overall costs of breast reconstruction. Therefore, to reduce the rate of TE removal, hospitalization, and costs, we created a standardized same-day multidisciplinary outpatient quality improvement protocol for diagnosing and treating patients with early signs of TE infection. METHODS: We prospectively evaluated 26 consecutive patients who developed a surgical site infection between February 2013 and April 2014. On the same day, patients were seen in the Plastic Surgery and Infectious Diseases clinics, underwent breast ultrasonography with or without periprosthetic fluid aspiration, and were prescribed a standardized empiric oral or intravenous antimicrobial regimen active against biofilm-embedded microorganisms. All patients were managed as per our established treatment algorithm and were followed up for a minimum of 1 year. RESULTS: TEs were salvaged in 19 of 26 patients (73%). Compared with TE-salvaged patients, TE-explanted patients had a shorter median time to infection (20 vs 40 days; P = 0.09), a significantly higher median temperature at initial presentation [99.8°F; interquartile range (IQR) = 2.1 vs 98.3°F; IQR = 0.4°F; P = 0.01], and a significantly longer median antimicrobial treatment duration (28 days; IQR = 27 vs 21 days; IQR = 14 days; P = 0.05). The TE salvage rates of patients whose specimen cultures yielded no microbial growth, Staphylococcus species, and Pseudomonas were 92%, 75%, and 0%, respectively. Patients who had developed a deep-seated pocket infection were significantly more likely than those with superficial cellulitis to undergo TE explantation (P = 0.021). CONCLUSIONS: Our same-day multidisciplinary diagnostic and treatment algorithm not only yielded a TE salvage rate higher than those previously reported but also decreased the rate of hospitalization, decreased overall costs, and identified several clinical scenarios in which TE explantation was likely.

Dual-Pedicle Flap for Unilateral Autologous Breast Reconstruction Revisited: Evolution and Optimization of Flap Design over 15 Years.

BACKGROUND: In thin patients or when a significant amount of skin is needed, use of the entire abdomen to reconstruct a single breast may be necessary. In this article, the authors present their 15-year experience in dual-pedicle flap evolution and optimization of flap design. METHODS: A retrospective review was conducted of all bipedicle flaps performed from 2000 to 2015. RESULTS: Overall, 57 patients (mean age, 49.2 years; mean body mass index, 26.2 kg/m) underwent dual-pedicle flap reconstruction of a unilateral mastectomy defect. Thirteen patients had a history of smoking, 30 patients had previously undergone irradiation, and 21 patients underwent immediate reconstruction. Eleven bipedicle flaps were performed with a pedicle transverse rectus abdominis musculocutaneous (TRAM) flap coupled to a free TRAM (n = 4), muscle-sparing TRAM (n = 4), or deep inferior epigastric artery perforator (DIEP) (n = 3) flap, and all were performed from 2000 to 2007. The thoracodorsal vessels (n = 8) were used more frequently earlier in the study period with the internal mammary vessels, whereas the antegrade/retrograde internal mammary vessels were used in the remaining patients, except for three patients in whom the internal mammary vessels and an internal mammary vessel perforator were used. Over the study period, there was an increase in the use of DIEP and superficial inferior epigastric artery flaps and the internal mammary vessels as recipients. Complications included delayed wound healing (n = 6), abdominal bulge (n = 2), cellulitis (n = 4), seroma (n = 3), and fat necrosis (n = 4). There was one partial flap loss where the superficial inferior epigastric artery portion of the dual-pedicle flap was lost. CONCLUSIONS: Dual-pedicle free flaps can be performed safely and reliably. Use of DIEP flaps maximizes pedicle length, and the internal mammary vessels can be used reliably in an antegrade and retrograde fashion to perfuse both components of the dual-pedicle flap. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Obese Women Experience Fewer Complications after Oncoplastic Breast Repair following Partial Mastectomy Than after Immediate Total Breast Reconstruction.

BACKGROUND: The authors hypothesized that obese patients would experience fewer complications after oncoplastic breast reconstruction following partial mastectomy than after immediate breast reconstruction following total mastectomy. METHODS: Complication rates were compared for oncoplastic breast reconstruction versus immediate breast reconstruction (with either implants or autologous tissue) in consecutive obese patients (body mass index ≥ 30 kg/m(2)) treated at a single center between January of 2005 and April of 2013. Logistic regression was used to analyze the associations between patient and surgical characteristics and postoperative outcomes. RESULTS: The study included 408 patients: 131 oncoplastic breast reconstruction and 277 immediate breast reconstruction patients. Presenting breast cancer stage was similar between the two groups. Oncoplastic breast reconstruction patients were older (55 years versus 53 years; p = 0.029), more obese (average body mass index, 37 kg/m(2) versus 35 kg/m(2); p < 0.001), and had more comorbidities. Nevertheless, the oncoplastic breast reconstruction group experienced fewer major complications requiring operative management (3.8 percent versus 28.5 percent; p < 0.001), fewer complications delaying adjuvant therapy (0.8 percent versus 14.4 percent; p < 0.001), and fewer incidences of hematoma/seroma formation (3.1 percent versus 11.6 percent; p < 0.004) than the immediate total breast reconstruction group. Univariate analysis found oncoplastic breast reconstruction to be an independent protector against major complications (OR, 0.1; p < 0.001) and complications that delayed adjuvant therapy (OR, 0.05; p = 0.002). CONCLUSION: Oncoplastic breast reconstruction likely represents a safer option than immediate total breast reconstruction following mastectomy for obese patients, particularly for patients who are superobese or present with preexisting medical comorbidities. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Lipofilling of the Breast Does Not Increase the Risk of Recurrence of Breast Cancer: A Matched Controlled Study.

BACKGROUND: Although many plastic surgeons perform autologous fat grafting (lipofilling) for breast reconstruction after oncologic surgery, it has not been established whether postoncologic lipofilling increases the risk of breast cancer recurrence. The authors assessed the risk of locoregional and systemic recurrence in patients who underwent lipofilling for breast reconstruction. METHODS: The authors identified all patients who underwent segmental or total mastectomy for breast cancer (719 breasts) (i.e., cases) or breast cancer risk reduction or benign disease (305 cancer-free breasts) followed by breast reconstruction with lipofilling as an adjunct or primary procedure between June of 1981 and February of 2014. They also then identified matched patients with breast cancer treated with segmental or total mastectomy followed by reconstruction without lipofilling (670 breasts) (i.e., controls). The probability of locoregional recurrence was estimated by the Kaplan-Meier method. RESULTS: Mean follow-up times after mastectomy were 60 months for cases, 44 months for controls, and 73 months for cancer-free breasts. Locoregional recurrence was observed in 1.3 percent of cases (nine of 719 breasts) and 2.4 percent of controls (16 of 670 breasts). Breast cancer did not develop in any cancer-free breast. The cumulative 5-year locoregional recurrence rates were 1.6 percent and 4.1 percent for cases and controls, respectively. Systemic recurrence occurred in 2.4 percent of cases and 3.6 percent of controls (p = 0.514). There was no primary breast cancer in healthy breasts reconstructed with lipofilling. CONCLUSIONS: The study results showed no increase in locoregional recurrence, systemic recurrence, or second breast cancer. These findings support the oncologic safety of lipofilling in breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Complications After Mastectomy and Immediate Breast Reconstruction for Breast Cancer: A Claims-Based Analysis.

OBJECTIVE: To evaluate complications after postmastectomy breast reconstruction, particularly in the setting of adjuvant radiotherapy. BACKGROUND: Most studies of complications after breast reconstruction have been conducted at centers of excellence; relatively little is known about complication rates in irradiated patients treated in the broader community. This information is relevant for decision making in patients with breast cancer. METHODS: Using the claims-based MarketScan database, we described complications in 14,894 women undergoing mastectomy for breast cancer from 1998 to 2007 and who underwent immediate autologous reconstruction (n = 2637), immediate implant-based reconstruction (n = 3007), or no reconstruction within the first 2 postoperative years (n = 9250). We used a generalized estimating equation to evaluate associations between complications and radiotherapy over time. RESULTS: Wound complications were diagnosed within the first 2 postoperative years in 2.3% of patients without reconstruction, 4.4% patients with implants, and 9.5% patients with autologous reconstruction (P < 0.001). Infection was diagnosed within the first 2 postoperative years in 12.7% of patients without reconstruction, 20.5% with implants, and 20.7% with autologous reconstruction (P < 0.001). A total of 5219 (35%) women received radiation. Radiation was not associated with infection in any surgical group within the first 6 months but was associated with an increased risk of infection in months 7 to 24 in all 3 groups (each P < 0.001). In months 7 to 24, radiation was associated with higher odds of implant removal in patients with implant reconstruction (odds ratio = 1.48; P < 0.001) and fat necrosis in those with autologous reconstruction (odds ratio = 1.55; P = 0.01). CONCLUSIONS: Complication risks after immediate breast reconstruction differ by approach. Radiation therapy seems to modestly increase certain risks, including infection and implant removal.

Current perspectives on radiation therapy in autologous and prosthetic breast reconstruction.

BACKGROUND: Postmastectomy radiation therapy (PMRT) has a well-established deleterious effect on both prosthetic and autologous breast reconstruction. The purpose of this study was to perform a literature review of the effects of PMRT on breast reconstruction and to determine predictive or protective factors for complications. METHODS: The MEDLINE and EMBASE databases were reviewed for articles published between January 2008 and January 2015 including the keywords "breast reconstruction" and "radiation therapy" to identify manuscripts focused on the effects of radiation on both prosthetic and autologous breast reconstruction. This subgroup of articles was reviewed in detail. RESULTS: Three hundred and twenty articles were identified and 43 papers underwent full text review. The 16 papers provided level III evidence; 10 manuscripts provided level I or II evidence. Seventeen case series provided level IV evidence and were included because they presented novel perspectives. The majority of studies focused on the injurious effects of radiation therapy and increased complications and concomitant lower patient satisfaction. CONCLUSIONS: Prosthetic based breast reconstruction and immediate autologous reconstruction are associated with lower patient satisfaction in the setting of radiation therapy. Autologous reconstructions can improve patient satisfaction as well as lower revision surgery and long term complications when performed in a delayed fashion after PMRT.

State of the art and science in postmastectomy breast reconstruction.

LEARNING OBJECTIVES: After reading this article, the participant should be able to: 1. Examine clinicopathologic factors to determine the best timing for breast reconstruction. 2. Develop treatment plans for all patients for breast preserving reconstruction. 3. Determine the best approaches for partial and whole breast reconstruction. 4. Be familiar with advanced techniques in breast reconstruction. BACKGROUND: Often, the decision to perform a partial or total mastectomy hinges on reconstructive issues, not oncology-related considerations. METHODS: Innovative timing and reconstruction approaches are being implemented after partial mastectomy and breast reconstruction after mastectomy. RESULTS: Among patients undergoing repair of a partial mastectomy defect, immediate or delayed repair before radiation allows for use of remaining breast tissue for repair. Innovative approaches include breast remodeling, local rotation advancement, and concentric mastopexy and breast reduction techniques to recontour remaining breast tissue. Delayed repair after whole-breast radiation usually is not preferred and is performed with autologous fat grafting or a flap. However, partial breast radiation allows for safe delayed repair after irradiation using the same techniques used for preradiation repair. The optimal timing for breast reconstruction after mastectomy remains a topic of controversy. Adjunct techniques for implant-based postmastectomy reconstruction include the use of acellular dermal matrix and autologous fat grafting, especially in the setting of radiation therapy. Techniques also include a more focused use of flaps only in the setting of radiation therapy with increasing use of new perforator-based autologous tissue flap options. CONCLUSION: Innovative approaches to breast reconstruction have evolved to provide restorative healing for patients and hasten return to their modern, active lifestyles.

Trends and variation in use of breast reconstruction in patients with breast cancer undergoing mastectomy in the United States.

PURPOSE: Concerns exist regarding breast cancer patients' access to breast reconstruction, which provides important psychosocial benefits. PATIENTS AND METHODS: Using the MarketScan database, a claims-based data set of US patients with employment-based insurance, we identified 20,560 women undergoing mastectomy for breast cancer from 1998 to 2007. We evaluated time trends using the Cochran-Armitage test and correlated reconstruction use with plastic-surgery workforce density and other treatments using multivariable regression. RESULTS: Median age of our sample was 51 years. Reconstruction use increased from 46% in 1998 to 63% in 2007 (P < .001), with increased use of implants and decreased use of autologous techniques over time (P < .001). Receipt of bilateral mastectomy also increased: from 3% in 1998 to 18% in 2007 (P < .001). Patients receiving bilateral mastectomy were more likely to receive reconstruction (odds ratio [OR], 2.3; P < .001) and patients receiving radiation were less likely to receive reconstruction (OR, 0.44; P < .001). Rates of reconstruction receipt varied dramatically by geographic region, with associations with plastic surgeon density in each state and county-level income. Autologous techniques were more often used in patients who received both reconstruction and radiation (OR, 1.8; P < .001) and less frequently used in patients with capitated insurance (OR, 0.7; P < .001), patients undergoing bilateral mastectomy (OR, 0.5; P < .001), or patients in the highest income quartile (OR, 0.7; P = .006). Delayed reconstruction was performed in 21% of patients who underwent reconstruction. CONCLUSION: Breast reconstruction has increased over time, but it has wide geographic variability. Receipt of other treatments correlates with the use of and approaches toward reconstruction. Further research and interventions are needed to ensure equitable access to this important component of multidisciplinary treatment of breast cancer.

Muscle-sparing TRAM flap does not protect breast reconstruction from postmastectomy radiation damage compared with the DIEP flap.

BACKGROUND: Irradiation to free flaps following immediate breast reconstruction has been shown to compromise outcomes. The authors hypothesized that irradiated muscle-sparing free transverse rectus abdominis musculocutaneous (TRAM) flaps experience less fat necrosis than irradiated deep inferior epigastric perforator (DIEP) flaps. METHODS: The authors performed a retrospective study of all consecutive patients undergoing immediate, autologous, abdomen-based free flap breast reconstruction with muscle-sparing free TRAM or DIEP flaps over a 10-year period at their institution. Irradiated flaps (external-beam radiation therapy) after immediate breast reconstruction were compared with nonirradiated flaps. Logistic regression analysis identified potential associations between patient, tumor, and reconstructive characteristics and surgical outcomes. RESULTS: The analysis included 625 flaps: 40 (6.4 percent) irradiated versus 585 (93.6 percent) nonirradiated. Mean follow-up for the irradiated and nonirradiated flaps was 60.0 and 48.5 months, respectively (p = 0.02). Overall complication rates were similar for both the irradiated and nonirradiated flaps. Irradiated flaps (i.e., both DIEP and muscle-sparing free TRAM flaps) developed fat necrosis at a significantly higher rate (22.5 percent) than the nonirradiated flaps (9.2 percent; p = 0.009). There were no differences in fat necrosis rates between the DIEP and muscle-sparing free TRAM flaps in both the irradiated and nonirradiated groups. CONCLUSIONS: Both DIEP and muscle-sparing free TRAM flap reconstructions had much higher rates of fat necrosis when irradiated. Contrary to our hypothesis, the authors found that immediate breast reconstruction with a muscle-sparing free TRAM flap does not result in a lower rate of fat necrosis than reconstruction with a DIEP flap. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Mechanisms of injury to normal tissue after radiotherapy: a review.

BACKGROUND: The benefits of radiotherapy for cancer have been well documented for many years, but many patients treated with radiation develop adverse effects. This study analyzed the current research into the biological basis of radiotherapy-induced normal tissue damage. METHODS: Using the PubMed and EMBASE databases, articles on adverse effects of radiotherapy on normal tissue published from January of 2005 through May of 2012 were identified. Their abstracts were reviewed for information relevant to radiotherapy-induced DNA damage and DNA repair. Articles in the reference lists that seemed relevant were reviewed with no limitations on publication date. RESULTS: Of 1751 publications, 1729 were eliminated because they did not address fundamental biology or were duplicates. The 22 included articles revealed that many adverse effects are driven by chronic oxidative stress affecting the nuclear function of DNA repair mechanisms. Among normal cells undergoing replication, cells in S phase are most radioresistant because of overexpression of DNA repair enzymes, while cells in M phase are especially radiosensitive. Cancer cells exhibit increased radiosensitivity, leading to accumulation of irreparable DNA lesions and cell death. Irradiated cells have an indirect effect on the cell cycle and survival of cocultured nonirradiated cells. Method of irradiation and linear energy transfer to cancer cells versus bystander cells are shown to have an effect on cell survival. CONCLUSIONS: Radiotherapy-induced increases in reactive oxygen species in irradiated cells may signal healthy cells by increasing metabolic stress and creating DNA lesions. The side effects of radiotherapy and bystander cell signaling may have a larger impact than previously acknowledged.

Impact of surgical techniques, biomaterials, and patient variables on rate of nipple necrosis after nipple-sparing mastectomy.

BACKGROUND: Nipple-sparing mastectomy is appropriate for selected patients with early-stage breast cancer or high breast cancer risk. However, the postoperative rate of nipple necrosis is relatively high (10 to 30 percent). This study analyzed the impact of clinicopathologic and surgical variables on partial and total nipple necrosis rates after nipple-sparing mastectomy and compared overall complication rates between nipple-sparing and skin-sparing mastectomy. METHODS: The study included 233 cases; 113 had nipple-sparing mastectomy and immediate breast reconstruction and 120 were matched cases of skin-sparing mastectomy and immediate reconstruction performed at the authors' institution from September of 2003 through May of 2011. RESULTS: The overall complication rate was 28 percent for nipple-sparing mastectomy and 27 percent for skin-sparing mastectomy (p > 0.99). In patients who did not have axillary surgery (those undergoing risk-reducing mastectomy), the overall rate was significantly higher in the nipple-sparing group (26 percent versus 9 percent; p = 0.06). However, in patients who had axillary surgery (either sentinel lymph node biopsy or axillary lymphadenectomy), the rate did not differ between the two groups. For nipple-sparing mastectomy, the overall incidence of any (partial or total) nipple necrosis was 20 percent. Only two cases (2 percent) had total necrosis. Larger breasts (C cup or larger) were associated with a higher rate of nipple necrosis (p = 0.003). CONCLUSIONS: The authors found no significant difference in the overall incidence of complications in patients who had nipple-sparing mastectomy or skin-sparing mastectomy. Exclusion of axillary lymphatic surgery in nipple-sparing mastectomy patients did not decrease the incidence of complications.

Acellular dermal matrix in irradiated tissue expander/implant-based breast reconstruction: evidence-based review.

BACKGROUND: The benefits of acellular dermal matrix for breast reconstruction have been well described. However, its clinical impact for breast reconstruction in the setting of radiation therapy has not been well reported. METHODS: The MEDLINE and EMBASE databases were reviewed for articles published between January of 2005 and February of 2012 on breast reconstruction using acellular dermal matrix in the setting of radiation therapy. The authors also reviewed their institutional experience of consecutive patients who met these criteria between January of 2008 and October of 2011. RESULTS: Thirteen articles were identified for review: three animal studies on acellular dermal matrix and 10 with level III evidence of its use in humans. The 10 clinical studies included 246 irradiated patients. The M. D. Anderson experience included 30 irradiated acellular dermal matrix patients for a total of 276 irradiated patients evaluated in this review. Use of acellular dermal matrix in implant-based breast reconstruction in the setting of radiation therapy did not predispose to higher infection or overall complication rates or prevent bioprosthetic mesh incorporation. However, the rate of mesh incorporation may be slowed. Its use allowed for increased intraoperative saline fill volumes, which improved aesthetic outcomes and allowed patients to awake from surgery with a formed breast. CONCLUSIONS: Use of acellular dermal matrix for implant-based breast reconstruction does not appear to increase or decrease the risk of complications, but it might provide psychological and aesthetic benefits. Multicenter or single-center randomized controlled trials that provide high-quality, level I evidence are warranted.

Current status of implant-based breast reconstruction in patients receiving postmastectomy radiation therapy.

BACKGROUND: Increasing numbers of patients with breast cancer are being treated with postmastectomy radiation therapy. The author reviewed the literature to determine the clinical impact of this increasing use of postmastectomy radiation therapy in patients with breast cancer who desire implant-based breast reconstruction. METHODS: The author searched the MEDLINE database for articles on breast reconstruction and radiation therapy published between January of 2008 and June of 2011 and reviewed the abstracts of those articles to identify articles with information about the impact of irradiation on implant-based breast reconstruction. This subgroup of articles was reviewed in detail. RESULTS: Two hundred eighty-five articles were identified. Nineteen articles were reviewed in detail. Eight articles provided level III evidence; one provided level I or II evidence from high-quality multicenter or single-center randomized controlled trials or prospective cohort studies. Two articles provided level IV evidence from case series and were included in the review because they offered a novel approach or perspective. The most recent studies find a significant need for unplanned or major corrective surgery in irradiated breasts reconstructed with implants. Although breast implant reconstruction in irradiated breasts is associated with high rates of complications, only a minority of patients require conversion to an autologous tissue flap. CONCLUSION: Although the majority of patients who undergo implant-based reconstruction and irradiation ultimately keep the implant reconstruction, patient surveys show that irradiation has a significantly negative effect on patient satisfaction.

Current status of autologous tissue-based breast reconstruction in patients receiving postmastectomy radiation therapy.

BACKGROUND: The threshold for patients with breast cancer to receive radiation therapy continues to be lowered. The author reviewed the literature to determine the clinical impact that the increasing use of radiation therapy has had on the management of patients with breast cancer who desire autologous tissue-based breast reconstruction. METHODS: The MEDLINE database was searched for articles on breast reconstruction and radiation therapy published between January of 2008 and June of 2011. Abstracts of those articles were reviewed to identify articles that addressed the most pressing radiation-related issues facing reconstructive breast surgeons performing autologous tissue-based reconstruction. This subgroup of articles was reviewed in detail. RESULTS: Two-hundred eighty-five articles were identified. Seventeen articles were reviewed in detail. Nine articles provided level III evidence, mostly from retrospective comparative studies. Five articles provided level I (n=2) or II (n=3) evidence from high-quality, multicenter or single-center, randomized, controlled trials or prospective cohort studies. Three articles provided level IV evidence from case series and were included in the review because they offered a novel approach or perspective. Since the author's last review of the literature in 2009, there have been changes in the practice patterns in the approach to autologous breast reconstruction in patients who undergo radiation therapy. CONCLUSION: With the increasing use of radiation therapy in patients with breast cancer, future studies should seek to provide more meaningful data (level I and II evidence) to help guide clinical decision-making. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.